Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/0001—Details of inhalators; Constructional features thereof
  • A61M15/002—Details of inhalators; Constructional features thereof with air flow regulating means
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/0001—Details of inhalators; Constructional features thereof
  • A61M15/0021—Mouthpieces therefor
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/0091—Inhalators mechanically breath-triggered
  • A61M15/0093—Inhalators mechanically breath-triggered without arming or cocking, e.g. acting directly on the delivery valve
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/0091—Inhalators mechanically breath-triggered
  • A61M15/0095—Preventing manual activation in absence of inhalation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M15/00—Inhalators
  • A61M15/08—Inhaling devices inserted into the nose

Definitions

• the present application concerns a flow control mechanism for inhalers, in particular breath-actuated medicinal inhalers.
• the application also relates to inhalers, and in particular to medicinal inhalers containing such flow control mechanisms.
• Conventional pMDI devices comprise a canister comprising an aluminium container sealed with a metering valve.
• the container contains the medicament formulation.
• the medicament formulation is a pressurized formulation containing either fine particles of one or more medicinal compounds suspended in a liquefied hydrofluoroalkane (HFA) propellant, or a solution of one or more medicinal compounds dissolved in a propellant/co-solvent system.
• HFA hydrofluoroalkane
• Other excipients may be included, e.g. surfactant, acid to act as a stabilizer, bulking agent.
• Formulations incorporating one drug in solution and another one in suspension form are also known.
• the sealed canister is provided to the patient in an actuator.
• the actuator is conventionally a generally L-shaped plastic moulding comprising a generally cylindrical vertical tube that surrounds the canister plus a generally horizontal tube that forms a patient portion (e.g., a mouthpiece or nosepiece) that defines an inspiration (or inhalation) orifice.
• a patient portion e.g., a mouthpiece or nosepiece
• an inspiration or inhalation orifice e.g., a mouthpiece or nosepiece
• Spacer devices have previously been devised which fit onto the mouthpiece of a pMDI in order to reduce the velocity of the emergent plume of medicament aerosol and to provide a volume in which it can expand and its propellant can evaporate more completely. This serves to avoid some of the problems of coordination and also avoids the tendency for high throat deposition caused by excessively fast drug particle inhalation.
• spacer devices are very bulky, and they can retain an excessive proportion of the drug on their walls, thereby reducing the dose that reaches the patient. Spacer devices can also be highly sensitive to electrostatic charge, which can often be strongly affected by the way in which they are washed or dried.
• pMDI medications should be taken with patients taking a slow and deep inhalation, normally interpreted as being less than 50-60 L/min.
• inhalation flow rate control varies from one user to another and even from one breath to another for the same patient.
• Some patients can sometimes achieve flow rates as high as 250 L/min., while others can sometimes achieve an order of magnitude less.
• Inhaling the medicament at a lower flow rate tends to reduce drug impaction in the upper airways and increases drug deposition deeper in the lung. If a patient is unable to control their asthma, or any other respiratory disease requiring use of an inhaler, this will impact their quality of life and may lead to the requirement for further medical intervention. This is clearly unfavourable.
• Inhaler designs each have their own inherent resistance (R) to air flow. This is often expressed in the units (Pa) 0 5 (min./L), and is related to inhalation air flow rate (FR) and patient- created pressure drop (PD) by the equation:
• flow governors and flow governor assemblies have been developed, e.g., as described in PCT Publication Nos. WO2017/1 12748; WO2017/1 12452 and WO2017/1 12400. These flow governors have the ability to change their geometry and resistance to air flow as a function of the pressure drop experienced, i.e., between an inlet and outlet of the flow governor.
• Flow governors (which can also be referred to as “flow rate limiters,” “flow limiters,” “flow regulators,” “flow limitation devices,” or derivations thereof) allow appreciable air flow rates at low differential pressures, while increasing air flow resistance at higher differential pressures in order to limit the air flow rates to values more consistent with those obtained at lower differential pressures to reduce inter-patient and intra-patient inhalation variability.
• TFR 15 ⁇ 5 L/min.
• GFR 30 ⁇ 5 L/min.
• such specifications are less than perfect, as they mean that GFR might have to be set unfavourably high and that TFR might have to be set unstably low. Additionally, even with such a gap between specifications, there is still the potential concern that out-of-specification circumstances might arise from time to time.
• an inhaler comprising:
• a breath actuated trigger mechanism reactive to an inhalation flow to trigger the release of a substance to be inhaled into the inhalation flow
• a flow governor arranged to govern inhalation flow through the first fluid flow path
• triggering the trigger mechanism reduces or blocks flow through the second fluid flow path.
• this configuration allows the TFR to be made closer to, or even greater than, the GFR.
• Both flow paths contribute to the inhalation flow pre-trigger, and as such allow a high TFR, a proportion of which is ungoverned.
• Closure (or partial closure) of the second flow path increases the proportion of the inhalation flow which is governed (up to 100%) which means that the GFR can be selected independently of the TFR.
• the second flow path is at least partially blocked by a part of the trigger mechanism after triggering.
• the inhaler defines a direction of actuation for a canister
• the valve seat faces a direction opposite to the direction of actuation
• the valve member moves in the direction of actuation to abut the valve seat.
• the valve member and valve seat are shaped to as to mate upon engagement; for example, the valve member may be convex, and the valve seat may be concave.
• this allows self-alignment of the components to form a good seal to block the flow to the extent desired.
• the trigger mechanism comprises a toggle mechanism for selectively permitting movement of the actuation member from its pre-triggered position to its post- triggered position.
• the toggle mechanism may comprise a vane positioned in the inhalation flow, the vane being moveable upon inhalation of a user to move the toggle mechanism between a primed condition in which the actuation member is maintained in its pre-triggered position by cooperation with the toggle mechanism and its post-triggered condition in which the toggle mechanism permits movement of the actuation member.
• the actuation member is an actuation arm that is pivotable about a pivot axis.
• the actuation arm is configured to at least partially block the second flow path at a position on the opposite side of the canister to the pivot axis. This allows the maximum range of motion to clear the valve seat in the pre-triggered position.
• the first flow path has a first flow inlet defined on the inhaler
• the second flow path has a second flow inlet defined on the inhaler, distinct from the first.
• the trigger mechanism is positioned downstream of the second flow path.
• the trigger mechanism when it triggers reduces or blocks flow through the second fluid flow path upstream of a canister outlet. This prevents the valve being clogged or rendered less effective by medicament.
• Both flow paths contribute to the inhalation flow pre-trigger, and as such allow a high TFR, a proportion of which is ungoverned. Closure (or partial closure) of the second flow path increases the proportion of the total inhalation flow which is governed (up to 100%), which means that the GFR can be selected independently of the TFR.
• a flow governor configured to govern at least part of the inhalation flow, the flow governor having a first condition and a second condition, in which in the second condition the flow governor is capable of governing a larger flow area than in the first condition;
• At least partially inhibiting the action of the flow governor pre- triggering means that there is a larger portion of the flow which is ungoverned before triggering.
• this configuration allows the TFR to be made closer to, or even greater than, the GFR.
• the flow governor comprises a flow governing member in which:
• the flow governing member is pivotable relative to a sidewall of a flow path, in which case in the first condition the flow governing member may be held in an open position in which it (or part of it) bears against the sidewall.
• the vane is pivotably mounted at a first end, and comprises a free end opposite the first end, in which in a rest condition of the vane, the free end is adjacent to the flow governor passageway.
• FIG. 4 is a detail perspective view of a part of the pMDI inhaler of FIG. 2;
• FIG. 6 is a first exploded view of a subassembly of the pMDI inhaler of FIG. 2, shown together with a canister;
• FIG. 9 is a perspective section view of the part of FIG. 8;
• FIGs. 10 and 11 are perspective views of a second part of the subassembly of FIG. 6;
• FIGs. 12 to 17 are perspective views of third to eighth parts of the subassembly of FIG.
• FIG. 19 is a perspective section view of the subassembly of FIG. 6 in an unactuated, rest condition, shown together with a canister and part of a canister loading mechanism for loading the canister;
• FIG. 20a is a section view of the subassembly of FIG. 6 in an unactuated, rest condition
• FIG. 21a is a perspective view of a flow governor component used in the pMDI inhaler of FIG. 2;
• FIGs. 21b and 21c are end views of a flow governor support component of the pMDI inhaler of FIG. 2 assembled with the flow governor component of FIG. 21a;
• FIGs. 24 and 25 are perspective views of parts of the subassembly of FIG. 23;
• FIG. 26 is a side view of part of the pMDI inhaler of FIG. 22;
• FIG. 27 is a section view of part of the pMDI inhaler of FIG. 22;
• FIG. 28 is a section view of a third pMDI inhaler in accordance with the present invention in a first condition.
• FIG. 29 is a section view of a third pMDI inhaler in accordance with the present invention in a second condition.
• FIG. 1 illustrates a conventional pressurized metered dose inhaler (pMDI) 50 comprising a valved container in the form of a canister 51 containing a medicament formulation 52, the canister comprising a can 53 sealed at a crimp 46 with a metering valve 54.
• the canister 51 sits within a housing (or "actuator") 55 comprising a tubular sleeve portion 56 having an open end 47 dimensioned to receive the canister 51 and from which its base 49 can protrude, and a portion in the form of a patient port 57 (e.g., in the form of a mouthpiece) that defines an inspiration orifice (or an air outlet) 45.
• a housing or "actuator” 55 comprising a tubular sleeve portion 56 having an open end 47 dimensioned to receive the canister 51 and from which its base 49 can protrude, and a portion in the form of a patient port 57 (e.g., in the form of a mouthpiece) that defines
• Such a patient port of an inhaler is sometimes referred to herein as a "mouthpiece" for simplicity.
• mouthpieces can instead be configured to be nosepieces of nasal inhalers and that the present disclosure can equally apply to nasal inhalers even where not specifically mentioned herein.
• the open upper end 47 of the housing 55 can define an aspiration orifice, or an air inlet, and the air outlet 45 can define an inhalation orifice, or an air outlet.
• FIGs. 2 to 4 show perspective views of a first pressurized metered dose inhaler (pMDI) 60 in accordance with the present invention.
• a housing 62 comprises a main housing body 63.
• a canister 61 (not shown in FIGs. 1 to 4) sits within the main housing body 63.
• the canister 61 is identical to the canister 51 of FIG. 1.
• the main housing body 63 comprises a generally tubular sleeve portion 64 dimensioned to receive and enclose the canister 61 and a portion in the form of a patient port 157 (e.g., in the form of a mouthpiece 65) that defines an inspiration orifice (or an air outlet) 145.
• the housing further comprises a mouthpiece cover 67 which is rotatably attached to the main housing body for movement between a first position (shown in FIGs. 2 and 3) in which the mouthpiece 65 is covered and a second position (FIG. 4) in which the mouthpiece 65 is uncovered.
• a first aspiration orifice, or an air inlet, 68 and a second aspiration orifice 69 are defined adjacent the mouthpiece 65.
• the first aspiration orifice 68 and the second aspiration orifice 69 are also covered, along with the mouthpiece 65, when the mouthpiece cover 67 is in its first position.
• FIG. 5 shows a partially exploded view of the pMDI 60.
• the main housing body 63 comprises a first part 70 and a second part 71. When assembled together, the first and second parts 70, 71 define a volume into which the canister 61 is received.
• the pMDI 60 comprises a canister actuation mechanism 72 positioned at an end of the housing 62 opposite to the mouthpiece 65, and a breath-actuated trigger mechanism 100 positioned proximate the mouthpiece 65. Both the canister actuation mechanism 72 and the breath-actuated trigger mechanism 100 control the actuation of the canister 61 to automatically dispense the canister contents as will be described below.
• FIGs. 6 and 7 show exploded views of the breath-actuated trigger mechanism 100 of the present invention.
• the trigger system 100 comprises a lower body component 165, a trigger mechanism chassis 101, a breath responsive member in the form of vane 110, a toggle link 120, an actuation arm 130, a fascia component 175, a flow governor support component 186 and a button component 140.
• the trigger mechanism 100 is configured to accept the canister 61.
• FIGs. 8 and 9 show views (FIG. 9 being a section view) of the trigger mechanism chassis 101.
• the trigger mechanism chassis 101 comprises a hollow tube forming the mouthpiece 157 defining the air flow outlet 145, a wall providing a swept arc 104, toggle axle tracks 105 which define follow-through tracks 106 and primary tracks 106a and axle location features 103.
• a flow governor passageway 190 is provided adjacent and below the mouthpiece 157 having an inlet opening 193 at the first air inlet 68.
• the trigger mechanism chassis 101 also provides a sheath 109 to retain the end of a spring, and comprises two semi -tubular location features 102.
• the trigger mechanism chassis 101 also comprises an upstanding wall 198 projecting radially from the swept arc 104.
• the wall 198 defines a series of flow passages 199 extending from the arc 104 to the free (upper) end of the wall 198. These flow passages 199 are formed adjacent the second air inlet 69.
• the flow passages 199 terminate in a first part 200 of a concave valve seat 203 (labelled in FIG. 18).
• the trigger mechanism chassis 101 is preferably injection moulded from a plastic material. It will be noted that the first and second inlets 68, 69 face in the same direction as the outlet 145. This means that the inspiration flow must change direction, and further is channelled past the outlet of the canister 61 (as will become apparent below).
• FIGs. 10 and 11 show the lower body component 165, comprising a nozzle block 159 defining a stem socket 160.
• the lower body component 165 also provides a chassis to support other components of the breath-actuated trigger mechanism.
• the lower body component 165 includes bearings 167 to receive actuation arm pivots.
• the lower body component 165 is preferably injection moulded from a plastic material.
• FIG. 12 shows the vane 110.
• the vane 110 comprises a curved vane wall with a vane pivot in the form of stub axles 111 at one end, and with toggle link pivot location features 112 formed some way along the vane wall from its end with the stub axles 111.
• the vane 110 also comprises a boss 113.
• the vane 110 is preferably injection moulded from a plastic material.
• FIG. 13 shows the toggle link 120.
• the toggle link 120 is in the form of a generally rectangular frame, comprising two side walls linked at the top by an upper bar 125 and linked at the bottom by a lower bar 123.
• the upper bar 125 is curved forwards and extends outwards at each end beyond the rectangular frame, the outward extensions being in the form of stub axles 122 bearing bosses 124.
• the lower bar 123 is curved downwards and extends outwards at each end beyond the rectangular frame, the outward extensions being a toggle pivot in the form of stub pivots 121.
• the toggle link 120 is preferably injection moulded from a plastic material.
• FIG. 14 shows the actuation arm 130.
• the actuation arm 130 is ring-shaped and has a vertical plane of symmetry.
• the actuation arm 130 bears two stub pivots 133 at a first end. Opposite the first end there is provided a radially outwardly extending tab 201 at a second end.
• the vertical plane of symmetry intersects the tab 201.
• a valve member 202 is provided at the free end of the tab 201.
• Two follow-through bosses 134 are provided between the pivots 133 and the tab 201. Next to each boss 134 is an integral spring arm 132.
• the actuation arm 130 is preferably injection moulded from a plastic material.
• the plastic material is preferably an acetal material.
• FIG. 15 shows the fascia component 175.
• the fascia 175 comprises a generally flat plate comprising an aperture 176 to receive the mouthpiece 157.
• the fascia 175 comprises two location features 177 that can engage with the tubular location features 102 on the trigger mechanism chassis 101.
• the fascia 175 also forms a first grill 194 between the location features 177.
• the first grill 194 defines a series of apertures 207.
• a second grill 195 is provided on the opposite side of the aperture 176 to the first grill 194.
• FIG. 15a shows the second grill 195 in more detail (FIG. 15a being a detail view of area "a" in FIG. 15).
• FIG. 16 shows the button component 140.
• the button component 140 comprises a protruding button 143 at one end, and two contact features 141 at the other end.
• the button component 140 also comprises two integral return spring arms 142.
• the button component 140 is preferably injection moulded from a plastic material. To confer appropriate properties to the spring arms 142, the plastic material is preferably an acetal material.
• the button component of FIG. 16 serves as an override feature that allows the patient to use the inhaler in a press-and- breathe mode, and may be used to prime the metering valve if required.
• the override enables the patient to use it to press forward against the back of the toggle mechanism 1 19 (which will be described below) (e.g., against the back of the vane) to move the vane to an angle past its trigger point.
• the toggle mechanism 1 19 will already be in an unlocked position but will still be forced into the actuated position (with the vane against the floor of the mouthpiece).
• the override button pressed the device will act similarly to a conventional press-and- breathe inhaler.
• FIG. 17 shows the flow governor support component 186.
• the flow governor support component 186 comprises a base 197 on which a collapsible silicone tube flow governor component (described below) can be mounted.
• the internal support structure of the flow governor is provided by two curved, part-elliptical support features 191 formed on the flow governor support component 186.
• the support features 191 are joined by a cross-member or cross-beam 189.
• the flow governor support feature extends upwards at its back into a wall with an aperture 187 in it. When the flow governor support component 186 is assembled onto the lower body component 165, this aperture 187 provides a location for the button 143 to protrude for access by the patient.
• FIG. 21a shows a flow governor component 310.
• the flow governor component 310 is a flexible tubular element constructed (in this embodiment) from a silicone material.
• the flow governor component 310 has a substantially uniform cross-sectional shape, which here is approximately an ellipse, e.g., a circle.
• FIGs. 18 to 20a show a breath-actuated trigger mechanism 100 assembled from the components shown in FIGs. 6 to 17, shown in its rest (unactuated) position.
• the trigger mechanism chassis 101 is attached to the lower body component 165, and the fascia 175 sits over the trigger mechanism chassis 101.
• the fascia component 175 and the trigger mechanism chassis cooperate such that the flow passages 199 and flow passages 204 cooperate to form flow paths from the apertures 205 (at the second fluid inlet 69) to the valve seat 203.
• the apertures 207 of the first grill 194 allow air flow from the first fluid inlet 68 into the flow governor passageway 190.
• the outer diameter of the base 197 is greater than an initial inner diameter of the flow governor component 310, and assembly of the two components can be achieved by stretching the flow governor component 310 over the base 197.
• This positioning results in the original (e.g., circular) cross-section of the tubular element 102 being deformed into an approximately elliptical (e.g., approximately elliptical with a greater aspect ratio than before) cross-sectional (i.e., in transverse cross-section) shape.
• the actuation arm 130 is mounted in the lower body component 165, the stub pivots 133 of the former being rotatably mounted in the bearings 167 of the latter for rotation about axis A.
• the front of the actuation arm 130 rests on the upper end of the toggle link 120 when the mechanism is at rest (FIG. 20a), with the spring arms 132 also contacting the toggle link 120.
• the vane 1 10 is mounted within the trigger mechanism chassis 101, with the vane's stub axles 11 1 engaged in the location features 103 of the trigger mechanism chassis 101 and with the vane's curved wall within the swept arc 104 of the trigger mechanism chassis 101.
• the vane can rotate relative to the chassis 101 about axis B (FIG. 20a).
• the toggle link 120 is also mounted within the trigger mechanism chassis 101, with its stub axles 122 in the toggle axle tracks 105 when the toggle link 120 is in its rest position.
• the vane 1 10 and toggle link 120 form the toggle mechanism 1 19 as will be described in further detail shortly.
• the stub pivots 121 at the bottom of the toggle link 120 are engaged with the toggle link pivot location features 1 12 on the back of the vane 1 10, the engagement being in the form of a rotatable hinge about an axis C (FIG. 20a).
• a spring 1 15 is provided (shown in FIG. 18 only), being a helical spring having a longitudinal axis of flexure. That is to say, the spring 1 15 has a centre line that runs along the centre of the helix from one end of the spring 115 to the other. That centreline (which need not be a straight line within the scope of the invention) defines the longitudinal axis along which the spring flexes. During flexing the shape of that longitudinal axis bends as the spring is loaded or unloaded. The primary reactionary force offered by the spring 115 results from longitudinal flexure rather than compression or extension of the spring along the line of the longitudinal axis.
• the spring 115 is mounted at a first end to the inside of the sheath 109 of the trigger mechanism chassis 101 and at a second end over the boss 113 on the vane 110.
• the spring 115 is slightly bent upwards in the centre by virtue of a deliberate misalignment between the boss 113 and the sheath 109. This bend provides a small residual spring force when the mechanism is at rest, thereby holding the vane 110 in the rest position, this force increasing the stability of the at-rest (e.g., primed, ready to trigger) mechanism slightly.
• a conventional pMDI canister 61 (shown in FIG. 19) is placed into the mechanism 100, with the tip of its stem 58 engaging with the stem socket 159, and with the underside of its metering valve contacting the two ledges 131 on the actuation arm 130.
• a force is applied to the canister 61.
• This may be direct (by a user's hand) or by means of energy stored in a spring or other resilient means.
• the actuation arm 130 is used to transmit the force, from the pMDI canister, to the trigger mechanism 100.
• resistance from the trigger mechanism 100 via the actuation arm 130 prevents the canister 61 from moving, and hence prevents the metering valve 54 from firing, until the toggle mechanism 119 is actuated.
• the actuation arm 130 contacts the ferrule of the pMDI canister approximately half way along its length and engages the toggle link 120 at its other end. This configuration results in reduction in the force that is applied to the toggle mechanism 119, giving an approximate additional mechanical advantage of 2: 1.
• the toggle mechanism 119 can resist a force from the canister of approximately twice its own resistive force.
• the actuation arm also has the spring arms 132 attached to it which act against the toggle link 120 and provide sufficient force to return the actuation arm 130 after actuation.
• the mechanism 100 At rest, as shown in FIGs. 19 and 20a, the mechanism 100 is stable, with the toggle link 120 supporting the load that the patient applies to the canister's base 49 via a deformed (e.g., compressed) resilient member 300.
• a first fluid flow path is shown as Fl in FIG. 20a, and a second as F2.
• Only the air outlet end of the flow governor component 310 is fixed and supported (i.e. by the base 197), whereas the air inlet end of the flow governor component 310 is freestanding and able to collapse onto the internal support structure.
• the primary function of the flow governor is to govern air flow when the patient inhales through the inhaler, limiting the patient's inspiratory flow rate to a narrow and controlled range in order to avoid excessively fast inhalation and consequently excessive mouth and throat drug deposition.
• the flow governor of the present disclosure is thus able to aid in the attainment of increased deep lung drug penetration and deposition.
• a flow governor allows patients with poor lung function (e.g., particularly poorly COPD patients) to experience a relatively low inhaler air flow resistance (allowing them to inhale sufficient air in a reasonable degree of comfort) while giving patients with stronger lungs a transiently higher air flow resistance to inhale against (thereby allowing them to inhale for longer and more deeply, while at the same time limiting their inhalation air flow rate to a level very similar to that of weaker patients).
• the inspiratory air flow rate can be kept much more consistent between patients and between inhalations. Medication delivery is thus much more predictable, allowing physicians to prescribe treatment regimes with an improved level of confidence.
• FIG. 21b illustrates the flow governor at rest (i.e., with the flow governor component 310 in an uncollapsed state).
• FIG. 21c shows the flow governor in an operative state (i.e., with the patient's inspiratory air flow substantially passing through it and with the flow governor component 310 in a collapsed state).
• the resultant reduction in the cross- sectional area of the air flow path leads to an increased resistance to air flow rate.
• the air flow path of the flow governor is only one part of the total overall resistance to air flow of the medicinal inhaler in which the flow governor is employed (e.g. it might be around 50% or less of the total inhaler air flow resistance if the inhaler has a moderate static resistance to air flow), then the mass flow rate of air through the flow governor does not fall in proportion to its reduced residual cross-sectional area.
• the flow governor 101 can be substantially bistable, where it tends to be in one of two states at any time: either it is in a substantially Open' or 'uncollapsed' state (FIG. 21b), or it is in a substantially 'collapsed' state (FIG. 21c).
• the finite stiffness of the flow governor component 310 means that small additional gaps are left around the corners of the internal support structure formed by the features 191 and cross-member 189 where the flow governor component 310 cannot bend sufficiently to close off all the small residual air passageways or gaps between the internal support structure and flow governor component 310 (see FIG. 21c).
• at least a minimum, or residual, air flow can always continue to flow. That is, the reduced pressure can never reach a value sufficient for the flow governor component 310 to collapse completely and to seal off all air flow through the flow governor.
• the flow governor is reactive to the flow rate of fluid through the first flow path Fl, and starts to narrow the lumen through the flow governor passageway as the flow rate increases (via the Venturi effect). Therefore, flow through the first fluid inlet 68 is governed.
• the flow through the second inlet 69 at the start of the second flow path F2 passes through the channels formed by the flow passages 199 and the flow passages 204 and enters the inhaler at the valve seat 203 which is fully open, as shown in Figure 18, when the trigger mechanism 100 is in its rest (unactuated) position.
• This second flow path F2 is not governed. Both flow paths converge and contribute to an inhalation flow IF.
• the user is free to inhale at a high flow rate (pre-triggering).
• air passes inwardly as described above, along the second flow path F2 and outwardly through the air outlet 145, causing a pressure drop across the two sides (convex and concave) of the curved wall of the vane 110.
• the flow path Fl also contributes to this inhalation flow IF, but is governed.
• the pressure drop caused by the inhalation flow IF causes the vane 110 to rotate about axis B, clockwise as drawn in FIGs. 20a / 20b, with its stub axles 1 1 1 rotating in the location features 103 of the trigger mechanism chassis 101.
• the actuated condition of the trigger mechanism 100 is shown in FIG. 20b, as compared to the unactuated condition of FIGs. 19 and 20a.
• the vane 1 10 sits against the base of the mouthpiece.
• the vane has been given a specific profile that allows it to sit against the floor of a conventional mouthpiece when actuated, yet to provide sufficient resistance to the airflow whilst in the rest position.
• the toggle link pivot location features 1 12 on the back of the vane 1 10 are displaced towards the open end of the mouthpiece 157.
• This displacement pulls the stub pivots 121 of the toggle link 120 forwards (i.e. towards the mouthpiece 157), thus unlatching the toggle linkage and overcoming the small restoring force from the bent spring 1 15 (shown in FIG. 18).
• the toggle linkage collapses, with the toggle link 120 moving generally downwards (compare FIGs. 20a and 20b).
• the movement of the toggle link 120 is steered by its bottom stub pivots 121 being pulled round about axis C by the rotational displacement of the toggle link pivot location features 1 12, and by its top stub axles 122 following the toggle axle tracks 105.
• the actuation arm 130 pushes the toggle link 120 down until its stub axles 122 leave the primary tracks 106a of the toggle axle tracks 105 and pass into their curved lower portions, i.e., into the follow-through tracks 106.
• the forwardly curved nature of these causes the stub axles 122 (and thence the top end of the toggle link 120) to move forward, out of the way of the actuation arm 130. This allows the actuation arm 130 to move downwards far enough to allow movement of the canister 51 as far as the total travel of the valve stem 58 into the metering valve 54.
• the actuation arm 130 will rotate about axis A to a point (shown in FIG. 20b) where the valve convex member 202 engages the concave valve seat 203 and prevents further significant ingress of air through the second fluid inlet 69. In other words, the flow path F2 is blocked.
• flow path Fl the majority (if not all) of the airflow into the inhaler is through flow path Fl : i.e., it is governed.
• the valve stem 58 is allowed to move far enough to release a dose of aerosolised medicament formulation.
• the breath-actuated trigger mechanism 100 allows "follow-through” of valve motion after its triggering point.
• the two follow-through bosses 134 obstruct the upper stub axles 122 and thus hold the toggle link 120 down, thereby preventing the toggle link 120 and the vane 110 from being reset by the vane return spring 115 until the load has been removed from the ledges 131 (e.g., when the load has been released from the canister).
• the two follow-through bosses 134 also serve to ensure that the toggle cannot ride over the top of the actuation arm 130 and thence wedge it down.
• the housing components 70, 71 provide an outer shell into which the breath-actuated trigger mechanism fits. They provide a more attractive and ergonomic form for the patient, and provide protection for the mechanism inside.
• a window opening 166 through which the button 143 on the button component 140 can protrude.
• This button 143 serves as a manual override: if a patient for any reason wishes to take a dose manually, rather than in breath-actuated fashion, then pressing on the button 143 causes the contact features 141 to push against the back of the vane 110, causing the vane to start to rotate as if breath actuated.
• the first step is that the load is removed from the base 49 of the pMDI canister 51, for example either by the patient unloading a firing spring (not shown) in a fully -automated breath-actuated inhaler or by the patient ceasing to press downwards on the base 49 of the pMDI canister 51.
• Removing the load from the pMDI canister allows the return spring in the valve 54 to reset the valve and allows the spring arms 132 to return the actuation arm 130 to its rest position.
• a bending pre-load force is imposed on it.
• a pre-load ensures that the mechanism will reset even at worst case component dimensional tolerances or if the device friction were to increase slightly due to wear or the presence of drug, dirt or moisture.
• a helical tension spring (not shown) - provides a low and relatively constant force that can be used to reset the mechanical pMDI breath- actuated trigger mechanism.
• the toggle mechanism 1 19 is designed not to go over-centre, but instead to be held by the friction generated in its stub axles 1 1 1 and stub pivots 121.
• the vane pivot in the form of stub axles 11 1 (rotatable about axis B in FIGs. 20a and 20b) is located close to the stub pivots 121 (rotatable about axis C) of the toggle link 120.
• the vane 1 10 pivots downwards towards the base of the mouthpiece.
• This follow-through is required to ensure that the pMDI valve can reach total travel, and greatly improves the mechanism's robustness to dimensional variations in the pMDI valve and canister.
• This follow-through ensures that the vane 1 10 is held against the base of the mouthpiece but allows an actuating arm to pass by it (i.e., that allows "follow-through") in order to dispense medicament.
• the rest position of the vane 1 10 is set at an angle (FIG. 20a) to help prevent airflow from leaking past the trigger mechanism. This also avoids any risk of clashing of the trigger mechanism with the vane 1 10, and therefore avoids adding unnecessary friction.
• the vane 1 10 provides a barrier to exhaled moisture and to bacteria and other undesirable entities in the exhaled breath: this is advantageous to protect the main parts of the inhaler should the patient unadvisedly exhale into it.
• a second pMDI 1060 in accordance with the invention is shown.
• the second pMDI is very similar to the first pMDI 60, and only the differences will be discussed here. Those differences lie in various components of the breath-actuated trigger mechanism 1 100 (as compared to the mechanism 100).
• the trigger system 1 100 comprises a lower body component 1 165, a trigger mechanism chassis 1 101, a breath responsive member in the form of vane 1 1 10, a toggle link 1 120, an actuation arm 1 130, a fascia component 1 175, a flow governor support component 1 186, a flow governor flap component 1220 and a button component 1 140.
• FIG. 24 shows the flow governor support component 1 186.
• the flow governor support component 1 186 comprises a base 1 197 having two opposed pivot receiving arms 1222. Each arm defines a concave pivot surface 1223 on a free end thereof. Additionally, the flow governor support component extends upwards at its back into a wall with an aperture 1 187 in it. When the flow governor support component 1 186 is assembled on to the lower body component 1 165, this aperture 1 187 provides a location for a button to protrude for access by the patient.
• FIG. 25 shows the flow governor flap component 1220.
• the flow governor flap component 1220 comprises a flap 1224 having a mounted end 1225 and a free end 1226. At either side of the mounted end 1225 there are provided two opposing stub shafts 1227 each of which has a curved, resilient leaf spring member 1228 extending therefrom. A stop member 1229 extends from the face of the flap 1224.
• FIGs. 26 and 27 show the assembled trigger system 1 100 from the side (FIG. 26) and in section (FIG. 27).
• the flap component 1220 is rotatably received against the flow governor support component 1 186 for rotation about an axis D.
• the stub shafts 1227 bear against the concave pivot surfaces 1223 at the end of the pivot receiving arms 1222 and are held in position by engagement with the trigger mechanism chassis 1 101.
• the spring arms 1228 bear against the mouthpiece component 1 101 (or more specifically, respective outwardly directed pegs 1 192 shown in FIG. 26) and are shown here in a loaded configuration.
• the flap 1224 sits within a flow governor passageway 1190 of the trigger mechanism chassis 1 101.
• the stop member 1229 prevents the flap 1224 from sitting against the wall of the passageway, out of the air flow.
• a flow path P exists past the free end of the flap 1224.
• the flap 1224 starts to rotate in a clockwise direction about D, deforming the spring arms 1228.
• the spring arms 1228 exert a generally anticlockwise (as drawn in FIG. 26) restorative force on the flap 1224 when it is rotated from its rest (no air flow) position.
• the second pMDI 1060 operates in the same way as the first. Specifically, the actuation arm 1 130 is configured to close an ungoverned bypass flow path upon triggering of the trigger system 1 100. As with the first embodiment, the second embodiment offers a largely ungoverned flow before triggering, and a governed flow after triggering.
• FIGs. 28 and 29 show side section views of a third breath-actuated pMDI inhaler 501 in accordance with the present invention.
• the inhaler 501 generally comprises a housing 450 containing a pMDI canister 506.
• the canister 506 has a valve with a stem 510 protruding therefrom.
• the stem 510 is engaged into a nozzle block 512 in the housing 450.
• the housing 450 further comprises a tubular sleeve portion 451 having an end 452 dimensioned to receive the inverted canister 506, and a portion in the form of a patient port 453 (e.g., in the form of a mouthpiece) that defines an inspiration orifice (or an air outlet) 526. Adjacent to the inspiration orifice 526 there is provided an air inlet 528 leading to a flow governor passage 461. The outlet 526 and the inlet 528 generally face in the same direction, such that the flow passage through the patient port 453 and the flow governor passage 461 are adjacent and generally parallel. It follows that the inspiration flow must almost reverse direction and flow past the nozzle block 512 when travelling from the inlet 528 to the outlet 526.
• the inhaler 501 comprises a priming mechanism 454, a triggering mechanism 455 and a flow governor 456.
• the priming mechanism 454 comprises a lever 504 protruding from the end 452 of the tubular sleeve portion 451 of the housing 450.
• the lever 504 is pivotable through about 90 degrees between a horizontal rest condition and a vertical primed condition (FIG. 28).
• the priming mechanism further comprises a caged compression spring 508 between the end of the lever 504 and the base of the inverted canister 506.
• the triggering mechanism 455 comprises a rocker 514, a catch 516, a vane 518 and a tension spring 520.
• the rocker 514 is rotatably mounted about a pivot 534.
• the rocker defines a first and second canister abutment 536, 538.
• the rocker 514 is biased in an anti -clockwise direction as shown in FIGs. 28 and 29 by the tension spring 520.
• the catch 516 is pivotably mounted to the rocker at a pivot 532 and defines a vane abutment 458.
• the vane 518 comprises a governor abutment 459 at its free lower end.
• the flow governor 456 comprises a flap 524 rotatable about a pivot 530.
• An arm 522 is connected to the flap 524 for rotation therewith. Operation
• the pMDI inhaler 501 is shown in a primed condition.
• the lever 504 has been rotated to compress the spring 508 against the base of the canister 506. Because the canister is held in position by its abutment on the rocker abutment 536, the canister cannot move and the spring compresses to store energy.
• the rocker 514 is prevented from pivoting clockwise on the rocker pivot 534, as it is constrained by the catch 516.
• the catch 516 is prevented from moving downward, or against rolling contact with the vane 518, by its vane abutment 458.
• the flap 524 is held in an open, or lower, position by the fact that the arm is constrained by the governor abutment 459 of the vane 518. In other words, the arm 522 is held captive against the bottom edge of the vane 518, so the flap 524 is unable to raise at this stage.
• Figure 29 shows the breath-actuated inhaler 501 in a fired condition.
• Lever 504 is still raised.
• the rolling contact of the top of the vane 518 with the vane abutment 458 of the catch 516 has caused the catch to slip off the top of vane and move downwards, allowing the rocker 514 to rotate clockwise. Movement of the rocker allows the canister 506 to move downwards under the force of the spring 508 and to compress the stem 510 into the canister.
• the resulting flow of medicament passes into the nozzle block 512 towards the fluid outlet 526.
• the canister 506 now rests on the second abutment 538 of the rocker, which is closer to the rocker pivot 534 than the first abutment 536.
• Rotation of the vane 518 makes it possible for the arm 522 of the governor 456 to rise under the influence of the Bernoulli forces created by the air flow past the upper surface of the flap 524. This, in turn, permits movement of the flap 524, leading to the air flow through the inlet 528 being governed.
• the third embodiment offers an ungoverned flow before triggering, and a governed flow after triggering.
• the flap 524 When the patient's inhalation eases off, the flap 524 returns to its rest position under gravity (this may also be achieved by employing a spring with very low force). Similarly, the vane 518 can return to the vertical position, again trapping the connected arm 522.
• bypass flow path F2 is completely blocked in the triggered condition. It will be noted that partial blocking or occlusion of the bypass flow path will also work to the desired effect, although complete blocking is preferable.
• the flow governor is shown to be completely immobilised in the pre-triggered condition. It will be understood that the movement of the flow governor member may instead be partially constrained: i.e., a limited degree of movement may be permitted.

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• Health & Medical Sciences (AREA)
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• 2017
  • 2017-05-04 GB GBGB1707095.4A patent/GB201707095D0/en not_active Ceased
• 2018
  • 2018-04-30 JP JP2019560127A patent/JP7088961B2/ja active Active
  • 2018-04-30 US US16/609,234 patent/US11707584B2/en active Active
  • 2018-04-30 WO PCT/US2018/030088 patent/WO2018204217A1/en unknown
  • 2018-04-30 CN CN201880029042.4A patent/CN110958898B/zh active Active
  • 2018-04-30 EP EP18794444.2A patent/EP3618907B1/en active Active

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